Chuxian Mai , Mayu Yamamoto , Hiroaki Shibahara , Qiong Wang , Atsushi Fukui
{"title":"高CD16-NKp46bright子宫内膜自然杀伤细胞可能预测复发性生殖失败妇女的妊娠成功。","authors":"Chuxian Mai , Mayu Yamamoto , Hiroaki Shibahara , Qiong Wang , Atsushi Fukui","doi":"10.1016/j.rbmo.2024.104756","DOIUrl":null,"url":null,"abstract":"<div><h3>Research question</h3><div>Could CD16<sup>-</sup>NKp46<sup>bright</sup> uterine endometrial natural killer (uNK) cells serve as a predictor of pregnancy success in women with unknown recurrent reproductive failure (URRF), and what are the underlying mechanisms involved?</div></div><div><h3>Design</h3><div>A prospective study involving 63 women with URRF, followed up for 2 years. After age adjustment, 17 women remained in both the pregnant and non-pregnant groups. The pregnant group was further divided into the live birth (<em>n</em> = 10) and miscarriage (<em>n</em> = 4) groups, with three women lost to follow-up. Surface antigens expressed and cytokine produced in uNK cells were analysed with multicolour flow cytometry.</div></div><div><h3>Results</h3><div>Expression NKp46<sup>+</sup> uNK (<em>P</em> = 0.034), NKp46<sup>bright</sup> uNK (<em>P</em> = 0.045), CD16<sup>-</sup>NKp46<sup>bright</sup> uNK (<em>P</em> = 0.026), NKp46<sup>bright</sup>NKG2D<sup>+</sup> uNK (<em>P</em> = 0.004) and NKp46<sup>+</sup>NKG2D<sup>+</sup> uNK (<em>P</em> = 0.037) cells was significantly lower in the non-pregnant group compared with the pregnant group. Also, the expression of CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells was significantly (<em>P</em> = 0.040) higher in the live birth group compared with the non-pregnant group. The threshold 44.9% of CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells showed the largest area under the curve. Women with decreased CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells (<44.9%), produced significantly higher TNF-α<sup>+</sup>IFN-γ<sup>+</sup> in CD56<sup>+</sup> uNK (<em>P</em> = 0.014) and in CD56<sup>bright</sup> uNK cells (<em>P</em> = 0.013) and significantly lower TNF-α<sup>-</sup>IFN-γ<sup>-</sup> in CD56<sup>+</sup> uNK (<em>P</em> = 0.039) and in CD56<sup>bright</sup> uNK cells (<em>P</em> = 0.017), and had an elevated risk of failing to achieve live birth or pregnancy (OR 21.60, 95% CI 2.14 to 218.58; <em>P</em> = 0.004 (OR 11.20, 95% CI 2.20 to 56.93; <em>P</em> = 0.005).</div></div><div><h3>Conclusions</h3><div>CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells are a protective factor as well as an appropriate candidate for predicting pregnancy success in URRF.</div></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":"50 6","pages":"Article 104756"},"PeriodicalIF":3.7000,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Higher CD16-NKp46bright uterine endometrial natural killer cells may predict pregnancy success in women experiencing recurrent reproductive failure\",\"authors\":\"Chuxian Mai , Mayu Yamamoto , Hiroaki Shibahara , Qiong Wang , Atsushi Fukui\",\"doi\":\"10.1016/j.rbmo.2024.104756\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Research question</h3><div>Could CD16<sup>-</sup>NKp46<sup>bright</sup> uterine endometrial natural killer (uNK) cells serve as a predictor of pregnancy success in women with unknown recurrent reproductive failure (URRF), and what are the underlying mechanisms involved?</div></div><div><h3>Design</h3><div>A prospective study involving 63 women with URRF, followed up for 2 years. After age adjustment, 17 women remained in both the pregnant and non-pregnant groups. The pregnant group was further divided into the live birth (<em>n</em> = 10) and miscarriage (<em>n</em> = 4) groups, with three women lost to follow-up. Surface antigens expressed and cytokine produced in uNK cells were analysed with multicolour flow cytometry.</div></div><div><h3>Results</h3><div>Expression NKp46<sup>+</sup> uNK (<em>P</em> = 0.034), NKp46<sup>bright</sup> uNK (<em>P</em> = 0.045), CD16<sup>-</sup>NKp46<sup>bright</sup> uNK (<em>P</em> = 0.026), NKp46<sup>bright</sup>NKG2D<sup>+</sup> uNK (<em>P</em> = 0.004) and NKp46<sup>+</sup>NKG2D<sup>+</sup> uNK (<em>P</em> = 0.037) cells was significantly lower in the non-pregnant group compared with the pregnant group. Also, the expression of CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells was significantly (<em>P</em> = 0.040) higher in the live birth group compared with the non-pregnant group. The threshold 44.9% of CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells showed the largest area under the curve. Women with decreased CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells (<44.9%), produced significantly higher TNF-α<sup>+</sup>IFN-γ<sup>+</sup> in CD56<sup>+</sup> uNK (<em>P</em> = 0.014) and in CD56<sup>bright</sup> uNK cells (<em>P</em> = 0.013) and significantly lower TNF-α<sup>-</sup>IFN-γ<sup>-</sup> in CD56<sup>+</sup> uNK (<em>P</em> = 0.039) and in CD56<sup>bright</sup> uNK cells (<em>P</em> = 0.017), and had an elevated risk of failing to achieve live birth or pregnancy (OR 21.60, 95% CI 2.14 to 218.58; <em>P</em> = 0.004 (OR 11.20, 95% CI 2.20 to 56.93; <em>P</em> = 0.005).</div></div><div><h3>Conclusions</h3><div>CD16<sup>-</sup>NKp46<sup>bright</sup> uNK cells are a protective factor as well as an appropriate candidate for predicting pregnancy success in URRF.</div></div>\",\"PeriodicalId\":21134,\"journal\":{\"name\":\"Reproductive biomedicine online\",\"volume\":\"50 6\",\"pages\":\"Article 104756\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive biomedicine online\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1472648324009453\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive biomedicine online","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1472648324009453","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Higher CD16-NKp46bright uterine endometrial natural killer cells may predict pregnancy success in women experiencing recurrent reproductive failure
Research question
Could CD16-NKp46bright uterine endometrial natural killer (uNK) cells serve as a predictor of pregnancy success in women with unknown recurrent reproductive failure (URRF), and what are the underlying mechanisms involved?
Design
A prospective study involving 63 women with URRF, followed up for 2 years. After age adjustment, 17 women remained in both the pregnant and non-pregnant groups. The pregnant group was further divided into the live birth (n = 10) and miscarriage (n = 4) groups, with three women lost to follow-up. Surface antigens expressed and cytokine produced in uNK cells were analysed with multicolour flow cytometry.
Results
Expression NKp46+ uNK (P = 0.034), NKp46bright uNK (P = 0.045), CD16-NKp46bright uNK (P = 0.026), NKp46brightNKG2D+ uNK (P = 0.004) and NKp46+NKG2D+ uNK (P = 0.037) cells was significantly lower in the non-pregnant group compared with the pregnant group. Also, the expression of CD16-NKp46bright uNK cells was significantly (P = 0.040) higher in the live birth group compared with the non-pregnant group. The threshold 44.9% of CD16-NKp46bright uNK cells showed the largest area under the curve. Women with decreased CD16-NKp46bright uNK cells (<44.9%), produced significantly higher TNF-α+IFN-γ+ in CD56+ uNK (P = 0.014) and in CD56bright uNK cells (P = 0.013) and significantly lower TNF-α-IFN-γ- in CD56+ uNK (P = 0.039) and in CD56bright uNK cells (P = 0.017), and had an elevated risk of failing to achieve live birth or pregnancy (OR 21.60, 95% CI 2.14 to 218.58; P = 0.004 (OR 11.20, 95% CI 2.20 to 56.93; P = 0.005).
Conclusions
CD16-NKp46bright uNK cells are a protective factor as well as an appropriate candidate for predicting pregnancy success in URRF.
期刊介绍:
Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients.
Context:
The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.